Ki-67 Antigen Immunostaining Research Articles

Impact of two different prostaglandin preparations on human corneal epithelial cells (HCE‐2) in in vitro conditions

AbstractPurpose To investigate impact of two antiglaucoma prostaglandin preparations on human corneal epithelial cells in in vitro conditions.Methods Human corneal epithelial cells (HCE‐2), cultured in standard conditions, were treated with two commercially available preparations of prostaglandins: latanoprost and tafluprost. Treatment was applied in two time points – parallel with cells plating (day 0) or after 48 hours from plating (day 2). Medium containing drugs with % concentration of 0.1, 0.3, 1, 3, 10 was changed every second day. As negative control standard medium was used, as positive – medium containing 3% methanol. After 48 hours of culture, living culture was stained with erythrosine to visualize dead cells. After fixation, immunostaining for Ki67 antigen and ubiquitin (proteasomal marker) was performed.Results In latanoprost group “day 0”, concentrations <1% affected cells attaching and proliferation rate, >1% made cells totally unable to attach. In tafluprost group “day 0”, concentrations <3% have shown no visible effect on cells, for concentrations >3%, fluctuations in cell shape appeared. In group “day 2” latanoprost treatment caused massive cells detachment for concentrations >1%. For lower concentration induced decrease of cells proliferation. Tafluprost treatment in this group showed no visible changes comparing with negative control, except 10% concentration, where induced mild cells detachment. In both groups treatment decreased expression of Ki67 and increased cellular ubiquitin (much more expressed in latanoprost group).Conclusion Latanoprost preparation revealed to be more harmful considering proliferation, proteolysis and toxicity for HCE‐2 cells in comparison to tafluprost.

Characterization of morphologically benign biologically aggressive meningiomas

Meningiomas are presently categorized into three grades by World Health Organization (WHO). Grade I, in general, is expected to behave in a benign fashion. However, a borderline group of grade I meningioma also exists, which may behave aggressively. To evaluate the proliferation index and p53 antigen expression of meningiomas and correlate with histological grade and clinical course. All 123 cases of meningiomas, diagnosed between January 2000 and August 2007, were regraded according to WHO 2000 criteria. Immunostaining for Ki-67 antigen and p53 protein were performed on 68 cases selected for the study. Six of the 68 cases presented with recurrence. Mean Ki-67 labeling index (Ki-67 LI) was 3.8%, 13.7%, 19.4% for grade I, II, and III cases, respectively. Multivariate analysis of mean Ki-67 LI showed statistically significant difference between subgroups. Mean p53 expression was found to be 15.5%, 57%, 60.8%, and 62.5% for grade I, II, III, and recurrent cases, respectively. Multivariate analysis of mean p53 expression showed no statistically significant difference between higher grades. All recurrent cases were histologically WHO grade I, and showed a high Ki-67 LI and p53 expression with mean Ki-67 LI and p53 expression of 8.6% and 62.5% respectively. Utilization of markers for proliferation and cell cycle regulators in combination with histopathological features helps in the identification of a subset of biologically aggressive morphologically benign meningiomas.

Growth Potential of Orbital Cavernous Hemangioma Suggested by Vascular Endothelial Growth Factor and its Receptor Flk-1

Orbital cavernous hemangiomas (CHs) manifest as slowly developing symptoms indicative of slow growth. The present study investigated the involvement of angiogenic factors and their receptors in the growth of orbital CHs. Surgical specimens of orbital CHs were obtained from nine patients. Formalin-fixed, paraffin-embedded specimens were stained immunohistochemically using antibodies against Ki-67, CD31, alpha-smooth muscle actin (alpha-SMA), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and VEGF receptors (flt-1 and flk-1). CD31 was expressed in the single layer of endothelial cells lining the vascular cavity. The thick vascular walls were positive for alpha-SMA, indicating that the vascular walls were smooth muscle cells. Ki-67 antigen immunostaining was mostly positive in the vascular walls and the staining index ranged from 0% to 6.8% (mean +/- standard deviation, 2.7 +/- 1.9%). VEGF and bFGF immunostaining were positive in all specimens. Flt-1 immunostaining was negative in all specimens, but flk-1 immunostaining was positive in both endothelial cells and smooth muscle cells. These results suggest that both VEGF and its receptor flk-1 are important in the growth of orbital CH.

Immunohistochemical detection of retinoblastoma protein and E2 promoter‐binding factor‐1 in ameloblastomas

To clarify the roles of cell cycle regulation in oncogenesis and cytodifferentiation of odontogenic tumors, expression of retinoblastoma protein (RB) and E2 promoter-binding factor-1 (E2F-1) was analyzed in ameloblastomas as well as in tooth germs. Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against RB, E2F-1, and phosphorylated RB. Ki-67 antigen immunostaining was made as a marker of cell proliferation. Immunohistochemical reactivity for RB, E2F-1, phosphorylated RB, and Ki-67 was detected in the nuclei of odontogenic epithelial cells near the basement membrane in tooth germs and benign and malignant ameloblastomas. The number of cells positive for phosphorylated RB was nearly equal to or slightly less than the number of cells positive for RB or E2F-1. The number of Ki-67-positive cells was slightly more than the numbers of cell positive for RB, E2F-1, or phosphorylated RB. The levels of immunoreactivity for RB, E2F-1, phosphorylated RB, and Ki-67 were slightly higher in benign and malignant ameloblastomas than in tooth germs. Plexiform ameloblastomas showed significantly higher expression of RB than follicular ameloblastomas. Ki-67 immunoreactivity was significantly higher in ameloblastic carcinomas than in metastasizing ameloblastomas. Similar immunoreactivity for RB, E2F-1, phosphorylated RB, and Ki-67 in tooth germs and ameloblastomas indicated cellular expression of phosphorylated RB and active-free E2F-1 in both normal and neoplastic odontogenic tissues. Expression of RB, E2F-1, and phosphorylated RB was considered to be involved in cell proliferation and differentiation of odontogenic epithelium via control of the cell cycle.

Evaluation of Cell Proliferation in Canine Tumors by the Bromodeoxyuridine Labeling Method, Immunostaining of Ki-67 Antigen and Proliferating Cell Nuclear Antigen

Cell proliferation activity and correlation between the LI (labeling index) of BrdU (5-bromo-2'-deoxy-uridine) and the expression of the Ki-67 antigen or PCNA (proliferating cell nuclear antigen) were evaluated by immunohistochemistry in 18 canine spontaneous neoplasms. Spearman's rank correlation coefficient and linear regression analysis revealed a significant correlation between the BrdU LI and Ki-67 LI, BrdU LI and PCNA LI, and BrdU LI and MI (mitotic index) in each case [rs = 0.917, P < 0.01 (BrdU LI vs. Ki-67 LI), rs = 0.736, P < 0.01 (BrdU LI vs. PCNA LI), rs = 0.748, P < 0.01 (BrdU LI vs. MI) by Spearman's rank correlation coefficient; and r = 0.918, P < 0.01 (BrdU LI vs. Ki-67 LI), r = 0.626, P < 0.01 (BrdU LI vs. PCNA LI), r = 0.763, P < 0.01 (BrdU LI vs. MI) by linear regression analysis]. Ki-67 LIs were more closely correlated with BrdU LIs than PCNA LIs or MIs, and the Ki-67 antigen is useful as an endogenous proliferation marker in canine neoplasms.

The relationship of the histologic grade at the deep invasive front and the expression of Ki‐67 antigen and p53 protein in oral squamous cell carcinoma

Although many histopathologic characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, accurate, and unequivocal factors have not been clearly identified. The purpose of this study was to evaluate a potential association between the histologic grade of malignancy at the deep invasive front and the expression of Ki-67 antigen and p53 protein in O-SCC. The expression of Ki-67 antigen and p53 at the invasive tumor front area of O-SCC was examined by immunohistochemistry of archived tissue from 62 cases. The mean age of patients was 60.7 years (range: 37-89) and the male-female ratio was 1.6:1 (38 men, 24 women). There were 20, 17, 14, and 11 cases classified as stage I to stage IV, respectively. The correlation between the intensity of immunostaining for Ki-67 antigen and p53 and the histologic grade of malignancy at the deep invasive front (invasive front grade, IFG) was analyzed. The expression of Ki-67 antigen and p53 in normal oral epithelia (10 cases) was also investigated. The mean Ki-67 labeling index (LI) in the O-SCC samples was 32.8 +/- 12.0% (n = 62). The mean total score of IFG (IFG score) was 9.1 +/- 2.7 points (n = 62). There was a significant linear correlation between the IFG score and the Ki-67 antigen (gamma = 0.651, R2 = 0.596, P < 0.0001). Of 50 tumors examined, 27 (54.0%) exhibited p53-positive nuclear immunostaining. The staining patterns for Ki-67 antigen and p53 were similar. Both Ki-67-LI and p53-positive status were significantly correlated with the IFG scores. The findings of this study demonstrate that overexpression of Ki-67 antigen and p53 at the deep tumor invasive front of O-SCC is associated with histologic grade of malignancy.

Pathological keratinisation in the conjunctival epithelium of Sjögren's syndrome

Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated. Conjunctival tissues or cells obtained from 12 SS patients and 13 normal subjects were subjected to indirect immunostaining to analyse expression of transglutaminase 1 (TGase1), involucrin, keratins 1, 4, 10 and 13. The number of proliferative cells was also analysed by immunostaining of Ki67 antigen. Additionally, changes in gene expression of TGase1 and involucrin after stimulation by IL-1 or IFN-gamma were quantified by real-time RT-PCR. TGase1 and involucrin were up-regulated in the conjunctival epithelium of SS patients. Although not statistically significant, Ki67 positive proliferative cells were slightly increased in SS patients. IFN-gamma stimulation significantly up-regulated TGase1 and unexpectedly repressed involucrin gene expression. IL-1 did not render any significant changes in the expression of these genes. These results suggest the existence of pathological keratinisation in the conjunctival epithelium of SS and also support our hypothesis that inflammatory cytokines may be involved in the ocular surface pathological changes in SS.

Basal ganglion hamartoma in a patient presenting with precocious puberty

We report a basal ganglion hamartoma in a 10-year-old boy in whom the major clinical feature was precocious puberty. Endocrinological evaluation showed a gonadotropin reaction to luteinizing hormone-releasing hormone with no elevation of the human chorionic gonadotropin beta-subunit level in the serum or cerebrospinal fluid. Neuroimaging studies showed a small, calcified, nonenhanced mass lesion with some cystic components in the right basal ganglion. Histopathological examination of specimens removed by stereotactic needle biopsy revealed disorganized neuronal and glial elements in the calcified gray matter-like lesion. In addition, although the presence of microcalcifications was not conspicuous, similar neuroglial lesions of various sizes were scattered in the surrounding white matter. Immunostaining for Ki-67 antigen (MIB-1) showed very low proliferative potential of the glial cells in all the lesions. To our knowledge, this is the first reported occurrence of an intracranial hamartoma located in a site other than the hypothalamus and causing precocious puberty. The possible mechanisms underlying the development of precocious puberty in this patient are discussed.

Prognostic Significance of Ki-67 Antigen Immunostaining (MIB-1 Monoclonal Antibody) in Ovarian Cancer

To assess the potential usefulness of Ki-67 antigen expression as a predictor of outcome in ovarian cancer through the analysis of MIB-1 monoclonal antibody reactivity. Cell proliferation and clinicopathologic variables were assessed in 26 patients with primary epithelial ovarian cancer who had undergone exploratory laparotomy. The expression of primary tumor proliferation related to Ki-67 antigen was immunohistochemically evaluated by MIB-1 monoclonal antibody. The value of Ki-67 labeling index (LI) ranged between 0 and 92.6% with a mean of 48.9%. Ki-67 LI correlated well with the mitotic index, but not the histological subtype. Ki-67 LI of more than 40%was defined as a higher proliferating tumor by a receiver operating characteristic curve analysis. Higher proliferating tumors were identified in 14 patients (54% of all subjects). The patients with higher proliferating tumors had a statistically significantly worse prognosis compared with those with lower proliferating tumors (p<0.001). The present study demonstrates that the proliferating index detected by Ki-67 antigen immunostaining is a useful factor for predicting the survival of patients with ovarian cancer.

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion ( p < 0.01) and distant metastasis ( p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher ( p < 0.01 and p < 0.001), and the AI was significantly lower ( p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus.

p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin.

Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied. We immunohistochemically examined the expression of tumor-related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method. Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible. The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression.

Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer.

MIB1 proliferation rate (MIB1-PR) and total S-phase fraction (SPF) were retrospectively determined in formalin-fixed, paraffin-embedded sections of 90 primary node-negative breast carcinomas. None of the patients had received adjuvant systemic therapy. Median follow-up in patients still alive at the time of analysis was 37.5 months (16-72 months). Immunostaining of Ki-67 antigen was performed using the monoclonal antibody MIB1 and the APAAP technique. An adjacent 50-microm paraffin section was used for flow cytometric S-phase determination. Results were compared to established clinicopathological prognostic factors. MIB1-PR was significantly correlated to grading (P = 0.018); SPF was significantly correlated with tumour size (P = 0.041) and inversely with steroid hormone receptor status (P = 0.03). A significant correlation between MIB1-PR and SPF was found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In univariate analysis, both MIB1-PR (optimized cut-off of 25%) and SPF (optimized cut-off of 8%) were significant prognostic factors for disease-free survival (DFS) (MIB1-PR, P = 0.0224; SPF, P = 0.0028). In multivariate analysis, however, only SPF remained significant; it was the strongest prognostic factor for DFS (P = 0.0073), stronger than MIB1-PR or established clinicopathological prognostic factors. We thus conclude that MIB1-PR and SPF provide additional prognostic information in node-negative breast cancer. However, in our study, flow cytometrically determined SPF had the greater prognostic impact.

Expression of the 67 KD laminin receptor in human cervical preneoplastic and neoplastic squamous epithelial lesions: an immunohistochemical study.

Interactions of cancer cells with laminin play a critical role during the progression of solid malignant tumours. Increased expression of the 67 kD laminin receptor (67LR), one of the several laminin binding proteins, is associated with the invasive and metastatic capacity of various types of cancer, including breast, colon, ovary, lung, and endometrial carcinoma. In this study, 67LR expression was analysed in a series of cervical biopsy specimens including 16 normal cervical tissues, 36 low-grade squamous intraepithelial lesions (SILs), 24 high-grade SILs, and 11 invasive carcinomas. Detection of the 67LR was performed using immunoperoxidase staining and the monoclonal antibody MLuC5 which specifically recognizes the 67LR. Immunostaining of the 67LR was correlated with human papillomavirus (HPV) type detected by in situ hybridization and with proliferative activity of the lesion determined by immunohistochemistry with the MIB-1 monoclonal antibody, specific for the Ki67 antigen. Increased expression of the 67LR was correlated with the histological severity of the lesions, with the strongest immunoreactivity being found in invasive carcinomas. Significant differences in 67LR expression were found between normal cervical epithelium and high-grade SILs (P < 0.05, non-parametric Mann-Whitney test) or invasive carcinomas (P < 0.001), as well as between low- or high-grade SILs and invasive carcinoma (P < 0.01 and P < 0.05, respectively). Ki67 antigen expression also increased with the severity of the lesions. There was a positive correlation for each type of lesion between expression of the 67LR and of the Ki67 antigen. No specific relationship was found between 67LR or Ki67 antigen immunostaining and HPV type detected in SILs, segregated into low-grade and high-grade lesions. These data add weight to the evidence that increased expression of the 67LR is a consistent, but not sufficient feature of the invasive and metastatic phenotype and suggest that high expression of the 67LR might be associated with both more proliferative and more aggressive cervical (pre)neoplastic lesions.

Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung

In lung carcinomas, the proliferative activity, as detected by Ki-67 antigen immunostaining of surgical specimens, is a valuable factor predicting clinical evolution and response to treatment. We investigated whether bronchial endoscopic and fine-needle aspiration (FNA) biopsies of lung carcinoma can provide a reliable estimation of the tumor proliferative fraction (TPF). In 66 resectable lung carcinomas, sections of preoperative bronchial or FNA biopsies and the corresponding surgical specimens were stained in parallel for Ki-67 using MIB-1 monoclonal. The mean TPF was 44.7% in the surgical specimens, 40.3% in bronchial biopsies, and 26.3% in FNAs. When the scores of biopsy and resected specimen of each individual tumor were compared, a significant correlation between the TPFs of preoperative and postoperative specimens was found ( r = .79). In both biopsy and surgical specimens, a high TPF was associated with squamous cell carcinoma histological type and high-grade (poorly differentiated) tumors. In addition, a significantly ( P < .05) lower diseasefree interval was found in patients affected by highly proliferating tumors (irrespective of the tumor stage). We conclude that the proliferative activity of lung cancer can be reliably assessed in bronchial or FNA biopsies. This information could help to select chemotherapy protocols in nonresectable lung carcinomas.

Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: A comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables

Prediction for malignancy of pancreatic endocrine tumors (PET) is often a formidable challenge for the pathologist. The authors evaluated the role of the proliferative activity and progesterone receptor protein (PgRP) in predicting prognosis and survival of PET. Twenty-three functioning (FT) and 31 nonfunctioning tumors (NFT) were evaluated for mitotic activity and immunostaining for Ki-67 antigen, proliferating cell nuclear antigen (PCNA), and progesterone receptor protein (PgRP) on paraffin sections. The results were expressed as a percentage (index) of immunoreactive or mitosing cells. All 54 cases showed immunostaining for Ki-67 and PCNA, and valuable mitotic index, whereas only a fraction of tumors (25 of 54 cases) exhibited PgRP expression. Ki-67 and PCNA indexes correlated strongly between themselves and to mitotic index, whereas an inverse relationship was observed between cell proliferation and PgRP status in both FT and NFT. Although univariate analysis showed that Ki-67, PCNA, mitotic and PgRP indexes, stage, immunoreactivity for hormones other than insulin, diameter, and nonfunctioning type of tumor were statistically correlated to survival, Cox's regression method let only Ki-67 index emerge as an independent predictor of survival using a cutoff value of 5% in both FT and NFT.

Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: Index of proliferative activity with prognostic significance: Garzetti G.G.; Ciavattini A.; Goteri G.; De Nictolis M.; Stramazzotti D.; Lucarini G.; Biagini G. ITA GYNECOL ONCOL 1995 56/2 (169–174)

Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: Index of proliferative activity with prognostic significance: Garzetti G.G.; Ciavattini A.; Goteri G.; De Nictolis M.; Stramazzotti D.; Lucarini G.; Biagini G. ITA GYNECOL ONCOL 1995 56/2 (169–174)

Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: Index of proliferative activity with prognostic significance

Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: Index of proliferative activity with prognostic significance

Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type.

A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell proliferation-associated antigen was immunohistochemically detected by the MIB-1 monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed cervical biopsies showing normal squamous epithelium or squamous metaplasia and in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was exclusively confined to the parabasal and basal layers of normal and metaplastic epithelium. There was no significant difference of Ki-67 antigen immunostaining between normal cervical biopsies and cases of squamous metaplasia. In SIL specimens, the staining was markedly increased in the parabasal and basal layers and Ki-67-positive cells were also distributed in the intermediate (low grade SIL) or all layers of epithelium (high grade SIL). Statistically significant differences for the density of Ki-67 antigen-labeled cells, which were assessed with an image analysis system, were found in comparisons between normal or metaplastic epithelium and SILs (P < .001) and between low grade SILs and high grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types, which were found in both low grade and high grade SILs, were significantly associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11 types that were found exclusively in low grade SILs. There was no significant difference found between the densities of Ki-67 antigen-labeled cells in HPV 16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of SILs taken as a whole or when segregating SILs into low grade and high grade.

Ki67 Antigen Immunostaining (MIB 1 Monoclonal Antibody) in Serous Ovarian Tumors: Index of Proliferative Activity with Prognostic Significance

The purpose of this study was to evaluate the biological significance of Ki67 antigen expression in serous ovarian tumors, through the analysis of MIB 1 monoclonal antibody reactivity in cystoadenomas, borderline tumors, and invasive cystoadenocarcinomas; the correlation between this index of cell proliferation and clinicopathologic parameters (FIGO stage and grade, and disease-free survival) was also investigated in invasive cystoadenocarcinomas. Fifty-four patients with serous ovarian tumors, treated at the Institute of Gynecologic and Obstetrics, Ancona University, Italy, were used as study population; 10 women had serous cystoadenoma, 16 women had serous borderline tumor, and 28 women had invasive cystoadenocarcinoma. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Compared to cystoadenomas and borderline tumors, the tissular Ki67 antigen immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 2 and 3 neoplasms ( P < 0.001). Within the cystoadenocarcinomas, a relationship was observed between the measured proliferation index and disease FIGO stage, but it was not significant ( P = 0.92). However, patients who recurred and/or had disease progression presented a primitive neoplasm with significantly higher expression of Ki67 antigen than that of patients with disease-free survival ( P = 0.01). A significant relationship was observed between the Ki67 index and disease-free survival, independent of histologic grade and stage, evaluated by Cox hazards analysis ( P = 0.02). The proliferation index detected by Ki67 antigen immunostaining may represent an indicator of aggressiveness in serous ovarian tumors and an additionally useful prognostic factor in cystoadenocarcinomas, probably independent of and apparently more significant than the tumor architectural grade and the disease FIGO stage.